Diabetes mellitus affects an estimated 10 million people in the US and is a major cause of blindness, renal failure, and vascular insufficiency leading to amputation. Diabetes is also intimately related to at least two other major health problems - obesity and atherosclerosis - and thus an understanding of both the basic mechanisms involved in this disease and approaches to its treatment have wide spread implications. This application is for a Diabetes and Endocrinology Research Center (DERC), the primary focus of which is the study of the etiology, pathogenesis and treatment of diabetes mellitus and its complications. Because of the multi-system nature of these disorders, the DERC will also provide support for research into a variety of problems, including obesity, other endocrine disorders, hormone synthesis and secretion, membrane protein chemistry, mechanisms of autoimmunity, regulation of cell growth and metabolism, etc. The primary aim of the DERC itself is to provide a stable and stimulating framework on which to conduct these multi-disciplinary studies. This will be accomplished through the three programs of the Center: 1. Core Laboratories: Five core laboratories (some of which contain subcores) will provide the basic support for cellular and molecular biology, clinical research, animal resources, radioligand assays, and administrative services. 2. Pilot and Feasibility Funds: Funds will be provided to support the development of new investigators, allow established investigators to explore new areas outside their basic expertise, and bring investigators with other expertise into the diabetes-endocrinology area. 3. Enrichment Program: An Enrichment Program consisting of seminar speakers, visiting professors and workshops will provide continuing education and stimulation, as well as format for cross-fertilization of our diversified research endeavors. Thus, the DERC will benefit research by providing a mechanism for coordinating, integrating and promoting inter-disciplinary activity among already active individual research groups. In addition, it will help build bridges between the Joslin and related institutions and bring new investigators into this important area of research. Finally, it will provide a mechanism for both stabilizing and building further a very productive environment for diabetes/endocrinology research.